Our initial goal is to construct and characterize a novel hybrid retrovirus efficiently expressing and utilizing a human virus envelope. Vectors we will develop based on this construct will be the first retroviral vectors capable of effective, safe and repeated genetic transfer into the human body without eliciting an immune response to the viral envelope. This constitutes an advance of significant medical impact in the field of gene therapy. In addition, we expect the described new retroviral vectors to have broad application and impact in the rapidly expanding fields of targeted gene delivery, viral vaccine development and cancer vaccine development. We have developed a novel hybrid retrovirus capable of using a human viral envelope which is the first demonstration of a functional envelope protein of this kind. Further functional envelope variants will be isolated by PCP, and cloned into the hybrid construct. The resulting retroviral constructs will be screened for increased efficiency of infection on cell lines optimal for infection with enveloped virions. The growth kinetics of selected viruses and their envelope protein expression and processing will be characterized in detail. PROPOSED COMMERCIAL APPLICATION: The potential commercial application of this research are: in health care and medicine, more specifically in gene therapy, anti-viral vaccines, and cancer vaccines.